Lithium Hydroxide → 6-(2,6-Difluoro-4-(1-methoxyethyl)phenyl)-5-fluoropicolinic acid

HRID 521928Notes

Reaction equation

HRID 521928 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH:8]([O:10][CH3:11])[CH3:9])[CH:5]=[C:4]([F:12])[C:3]=1[C:13]1[N:18]=[C:17]([C:19]([O:21]C)=[O:20])[CH:16]=[CH:15][C:14]=1[F:23].[OH-].[Li+]>CO.O>[F:1][C:2]1[CH:7]=[C:6]([CH:8]([O:10][CH3:11])[CH3:9])[CH:5]=[C:4]([F:12])[C:3]=1[C:13]1[N:18]=[C:17]([C:19]([OH:21])=[O:20])[CH:16]=[CH:15][C:14]=1[F:23]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86713867Methyl 6-(2,6-difluoro-4-(1-methoxyethyl)phenyl)-5-fluoropicolinate

Product 1

HCID 900724756-(2,6-Difluoro-4-(1-methoxyethyl)phenyl)-5-fluoropicolinic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of methyl 6-[2,6-difluoro-4-(1-hydroxyethyl)phenyl]-5-fluoro-pyridine-2-carboxylate (1.21 mmol, 376 mg; penultimate intermediate en route to Intermediate 136) in N,N-dimethylformamide (50 mL) at 0° C. was added sodium hydride (60 mass % in mineral oil, 1.5 equiv., 1.81 mmol, 72.5 mg). The mixture was stirred for 2 minutes, then iodomethane (3.0 equiv., 3.62 mmol, 0.226 mL) was added. The reaction mixture was stirred at room temperature for 2 days. The reaction mixture was quenched with water and extracted with EtOAc. The organic layer was washed with brine, dried (Na2SO4) and concentrated. The residue was purified on silica eluted with 0 to 50% EtOAc in Heptane to provide methyl 6-(2,6-difluoro-4-(1-methoxyethyl)phenyl)-5-fluoropicolinate (392 mg, 63%). This ester was diluted with MeOH (15 mL) and water (5 mL) and lithium hydroxide (60 mg) was added. The mixture was stirred overnight at rt. The reaction was quenched by the addition of 1 N HCl(aq), then the mixture was diluted with EtOAc and washed with brine. The organic extracts were dried (Na2SO4) and concentrated in vacuo to provide the title compound (quant) which was used without purification.

Workup

  1. additionwas added
  2. customThe reaction was quenched by the addition of 1 N HCl(aq)
  3. additionthe mixture was diluted with EtOAc
  4. washwashed with brine
  5. dry with materialThe organic extracts were dried (Na2SO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a29b660f94e94923a975c7b7ed92269d
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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